331244-89-4

Usage

Uses

Used in Cancer Treatment:
BAM7 is used as an activator of the proapoptotic BAX protein for cancer treatment. By selectively activating BAX, BAM7 promotes apoptosis in cancer cells, which can be an effective strategy in combating various types of cancer.
Used in Pharmaceutical Research:
BAM7's ability to induce apoptosis in cancer cells makes it a valuable compound for pharmaceutical research. It can be further studied and potentially developed into a drug candidate for the treatment of cancer, contributing to the development of novel therapeutic approaches in oncology.

Biological Activity

bam7 is a direct and selective activator of bax with ic50 value of 3.3um [1].in the competitive fluorescence polarization assay (fpa), bam7 competes with fitc–bim sahb for bax binding site(bh3) in a dose dependent manner. bam7 shows no antiapoptotic or bakδc competitive binding interactions even at 50 μm dosing, revealing a remarkable selectivity of bam7 for bax. the interaction between bam7 and bax at the very surface induces the characteristic structural changes that yield functional bax oligomerization. in the in vitro assay, bam7 induces bax-dependent cell death but not the cells with bak. bam7 could be developed to a new generation of apoptotic modulators that directly activate bcl-2 family executioner proteins in cancerand other diseases driven by pathologic apoptotic blockades [1].

Biochem/physiol Actions

BAM7 is a selective activator of BAX, a proapoptotic member of the BCL-2 protein family. BAM7 binds directly to the BAX trigger site, a distinct BH3 binding site that regulates BAX activation, inducing BAX oligomerization, which enables the release of apoptogenic factors that result in cell death. BAM7 is selective for this previously unknown BH3-binding groove on the N-terminal face of BAX.

references

[1] evripidis gavathiotis, denis e reyna, joseph a bellairs, elizaveta s leshchiner, and loren d walensky. direct and selective small-molecule activation of proapoptotic bax. nat chem biol. 2012 july ; 8(7): 639–645.

Synthetic route

α-bromoacetophenone (70-11-1) + 4-<(2-ethoxyphenyl)hydrazono>-N'-thiocarbamoyl-3-methyl-2-pyrazolin-5-one → 4-(2-(2-ethoxyphenyl)hydrazono)-3-methyl-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5(4H)-one (331244-89-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol at 80℃;

ortho-phenitidine (94-70-2) → 4-(2-(2-ethoxyphenyl)hydrazono)-3-methyl-1-(4-phenylthiazol-2-yl)-1H-pyrazol-5(4H)-one (331244-89-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium nitrite; hydrogenchloride / water 1.2: 20 °C 2.1: acetic acid / Reflux 3.1: N-ethyl-N,N-diisopropylamine / ethanol / 80 °C View Scheme

Upstream product

• 94-70-2 ortho-phenitidine 
• 70-11-1 α-bromoacetophenone 

Relevant academic research and scientific papers

PYRAZOL-3-ONES THAT ACTIVATE PRO-APOPTOTIC BAX

This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells).